ANTIPROLIFERATIVE EFFECTS OF LOW-DOSE MICRONIZED PROGESTERONE

Objective: To study the pharmacodynamic effects of oral micronized P o n endometrial maturation. Design: This was a controlled, open, paralle l group, pilot study. Setting: The experiment was performed in an outp atient academic clinical research unit. Patients: Twelve healthy, P-ch allenged, estrogen-primed, postmenopausal women participated in the st udy. Interventions: Patients were given 300 mg micronized P daily (8:0 0 A.M.) or twice (8:00 A.M. and 4:00 P.M.) daily from study days 1 thr ough 14 after estrogen priming for 30 days. Blood samples were taken a t 0, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours after the 8:00 A.M. dose on study day 1 and 14 and again at 8:00 and 9:30 A.M. on days 3 and 5 fas ting, days 7 and 9 after a fatty meal, and day 11 after a high fiber m eal. Endometrial biopsies were taken on day 1 and 14.Main Outcome Meas ures: Progesterone concentrations were measured. Endometrial biopsies were studied for effects on histology, glycogen content of glands, rib osomal RNA, and nuclear estrogen receptors in glands, surface epitheli um, and stroma. Results: Day 1 and 14 P kinetics were similar for 8 ho urs. Dose-dependent increases in glandular glycogen, decrease in ribos omal RNA, and decrease in nuclear estrogen receptors were demonstrated . Conclusions: Oral micronized P can induce antiproliferative changes in the human endometrium at doses lower than those required for transf ormation of the endometrium to a full secretory state.